Protein Structure and Function: Applications of Bioinformatics Methods - John Rigden 2014

Comparative Protein Structure Modeling
Introduction
Sequences, Structures, and Structural Genomics

The Structure/175.html">Implementation of large-scale genome sequencing projects has resulted in approximately six million unique sequences being known to date (Apweiler et al. 2004; S. N. Wu et al. 2006). If metagenomic data from the “Craig Venter’s Global Ocean Survey” project are added to this information from public Databases, the number of known sequences doubles (Rusch et al. 2007; Venter et al. 2004; Yooseph et al. 2007). At the same time, the number of Proteins whose three-dimensional structure has been determined experimentally using X-ray crystallography or nuclear magnetic Resonance (NMR) spectroscopy is only about 50,000. Because experimental structure determination techniques are complex and time-consuming, the proportion of proteins with experimentally determined Spatial Models will continue to shrink, dropping below the current value of 1%. To bridge the gap between the number of known sequences and spatial models, computational Methods must be applied.

In 2000, structural Genomics projects were launched worldwide. One of the key goals was to experimentally determine the three-dimensional structure of several thousand carefully selected protein sequences with unknown structures. Structures determined in this manner could then be used as templates for computational modeling of proteins with similar sequences. The number of such related proteins exceeds the number of experimentally determined structures by a factor of 100 (Burley et al. 1999). These widespread efforts have become the primary source of experimentally solved protein structures: 75% of the novel folds deposited in the PDB in recent years resulted from structural genomics initiatives (Burley et al. 2008). At the same time, such experimental studies emphasize The Importance of theoretical structure-modeling methods, given that over 99% of the spatial models yet to be built will be generated using computational approaches (Manjasetty et al. 2007).